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首度證實環狀RNA於人類全能性幹細胞及體細胞重編程之功能與生成機制

Nature Communications 8, Article number: 1149 (2017) doi:10.1038/s41467-017-01216-w

http://www.nature.com/articles/s41467-017-01216-w

Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuated the downregulation of these target genes and suppressed hESC differentiation. We further identified hESC-enriched splicing factors and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the splicing factor ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA “sponge” to regulate the molecular circuitry, which modulates human pluripotency and differentiation.

 


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115台北市南港區研究院路二段128號
Tel: 02-27899515
Fax: 02-27858059
icob@gate.sinica.edu.tw
Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:1029504--
 瀏覽人數:1029504